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Deep learning algorithms have recently been developed that utilize patient anatomy and raw imaging information to predict radiation dose, as a means to increase treatment planning efficiency and improve radiotherapy plan quality. Current state-of-the-art techniques rely on convolutional neural networks (CNNs) that use pixel-to-pixel loss to update network parameters. However, stereotactic body radiotherapy (SBRT) dose is often heterogeneous, making it difficult to model using pixel-level loss. Generative adversarial networks (GANs) utilize adversarial learning that incorporates image-level loss and is better suited to learn from heterogeneous labels. However, GANs are difficult to train and rely on compromised architectures to facilitate convergence. This study suggests an attention-gated generative adversarial network (DoseGAN) to improve learning, increase model complexity, and reduce network redundancy by focusing on relevant anatomy. DoseGAN was compared to alternative state-of-the-art dose prediction algorithms using heterogeneity index, conformity index, and various dosimetric parameters. All algorithms were trained, validated, and tested using 141 prostate SBRT patients. DoseGAN was able to predict more realistic volumetric dosimetry compared to all other algorithms and achieved statistically significant improvement compared to all alternative algorithms for the V 100 and V 120 of the PTV, V 60 of the rectum, and heterogeneity index.

The health-care industry is a substantial contributor to global greenhouse gas emissions, yet the specific environmental impact of radiotherapy, a cornerstone of cancer treatment, remains under-explored. We aimed to quantify the emissions associated with the delivery of radiotherapy in the USA and propose a framework for reducing the environmental impact of oncology care. In this multi-institutional retrospective analysis and simulation study, we conducted a lifecycle assessment of external beam radiotherapy (EBRT) for ten anatomical disease sites, adhering to the International Organization for Standardization's standards ISO 14040 and ISO 14044. We analysed retrospective data from Jan 1, 2017, to Oct 1, 2023, encompassing patient and staff travel, medical supplies, and equipment and building energy use associated with the use of EBRT at four academic institutions in the USA. The primary objective was to measure the environmental impacts across ten categories: greenhouse gases (expressed as kg of carbon dioxide equivalents [CO2e]), ozone depletion, smog formation, acidification, eutrophication, carcinogenic and non-carcinogenic potential, respiratory effects, fossil fuel depletion, and ecotoxicity. Human health effects secondary to these environmental impacts were also estimated as disability-adjusted life years. We also assessed the potential benefits of hypofractionated regimens for breast and genitourinary (ie, prostate and bladder) cancers on US greenhouse gas emissions using an analytic model based on the 2014 US National Cancer Database for fractionation patterns and patient commute distances. We estimated that the mean greenhouse gas emissions associated with a standard 25-fraction EBRT course were 4310 kg CO2e (SD 2910), which corresponded to 0·0035 disability-adjusted life years per treatment course. Transit and building energy usage accounted for 25·73% (1110 kg CO2e) and 73·95% of (3190 kg CO2e) of total greenhouse gas emissions, respectively, whereas supplies contributed only 0·32% (14 kg CO2e). Across the other environmental impact categories, most of the environmental impact also stemmed from patient transit and energy use within facilities, with little environmental impact contributed by supplies used. Hypofractionated treatment simulations suggested a substantial reduction in greenhouse gas emissions—by up to 42% for breast and 77% for genitourinary cancer—and environmental impacts more broadly. This comprehensive lifecycle assessment of EBRT delineates the environmental and secondary health impacts of radiotherapy, and underscores the urgent need for sustainable practices in oncology. The findings serve as a reference for future decarbonisation efforts in cancer care and show the potential environmental benefits of modifying treatment protocols (when clinical equipoise exists). They also highlight strategic opportunities to mitigate the ecological footprint in an era of escalating climate change and increasing cancer prevalence. Mount Zion Health Fund.

Modernisation of the American Joint Committee on Cancer and Union for International Cancer Control (AJCC/UICC) staging for HPV-positive oropharyngeal carcinoma has strengthened its fundamental role to convey prognosis and guide treatment decisions. Implementation has nonetheless revealed imbalances. An AJCC committee reappraised HPV-positive oropharyngeal carcinoma pathological staging to advance prognostic accuracy and improve clinical applicability. For this analysis, US registry data from the National Cancer Database were divided into derivation and validation cohorts. Eligible cases encompassed surgically treated adult patients aged 18 years or older with HPV-positive oropharyngeal carcinoma. The primary objective was to derive and validate an optimised HPV-positive oropharyngeal carcinoma pathological staging classification based on determinants of overall survival. Multivariable Cox regression models were used to assess lymph node characteristics for overall survival. Non-linear associations between metastatic lymph node number and survival were modelled with restricted cubic splines. Adjusted hazard ratios (AHRs) and recursive partitioning analysis methods were applied to generate optimal classification groups. Performance was evaluated with Groome's criteria. Overall, 14 447 patients across 984 facilities in the USA met the criteria for inclusion, and were divided into a derivation cohort (n=7768) and validation cohort (n=6679). Patients were treated between 2010 and 2019; 12 276 (85·0%) were male, 2171 (15·0%) were female, 13 594 (94·1%) were White, and 4552 patients (31·5%) had pathological extranodal extension (pENE). Median follow-up was 52·4 months (95% CI 51·5–53·3). Mortality risk increased with each additional metastatic lymph node (HR 1·20 [95% CI 1·11–1·29], p<0·0001), up to an optimal cutoff at 4·3 lymph nodes. Multivariable analysis confirmed the association of pENE with increased mortality risk (HR 1·47 [95% CI 1·30–1·65], p<0·0001), but no significant prognostic changes were shown by the extent of pENE (minor vs major). AHR approaches derived and validated optimised pN and pTNM stage categories (N1a: 1 positive lymph node and pENE-negative; N1b: 2–4 positive lymph nodes and pENE-negative; N2: >4 positive lymph nodes and pENE-negative or 1–4 positive lymph nodes and ENE-positive; N3: >4 positive lymph nodes and ENE-positive; Stage I: T0-2N0-1M0; Stage II: T0-2N2-3M0 or T3N0-2M0; Stage III: T3N3M0 or T4N0-3MO); Stage IV: M1. AJCC9V showed superior hazard consistency, outcome prediction, and balance, but not hazard discrimination, compared to AJCC8E. The AJCC Expert Panel on HPV-positive oropharyngeal carcinoma endorsed the proposal by Delphi consensus. The AJCC9V HPV-positive oropharyngeal carcinoma staging classification confers an improved schema for guiding prognostication and management compared to AJCC8E. Incorporating ENE and correcting imbalances will enhance clinical relevance and align pathological staging in a condition whose management continues to evolve. None.

Transparent and precise endpoint definitions are a crucial aspect of clinical trial conduct and reporting, and are used to communicate the benefit of an intervention. Previous studies have identified inconsistencies in endpoint definitions across oncological clinical trials. Here, the Head and Neck Cancer International Group assessed endpoint definitions from phase 3 trials or trials considered practice-changing for patients with recurrent or metastatic mucosal head and neck squamous cell carcinoma, published between 2008 and 2021. We identify considerable and global heterogeneity in endpoint definitions, which undermines the interpretation of results and development of future studies. We show how fundamental components of even incontrovertible endpoints such as overall survival vary widely, highlighting an urgent need for increased rigour in reporting and harmonisation of endpoints.

Robust time-to-event endpoint definitions are crucial for the assessment of treatment effect and the clinical value of trial interventions. Here, the Head and Neck Cancer International Group investigated endpoint use in phase 3 trials and trials considered potentially practice-changing published between 2008 and 2021 in the curative-intent setting for patients with mucosal head and neck squamous cell carcinoma. Of the 92 trials reviewed, we show that all core components of endpoint reporting were heterogeneous, including definitions of common terms, such as overall survival and progression-free survival. Our report highlights the urgent need for harmonisation of fundamental components of clinical trial endpoints and the engagement of all stakeholders to ensure the transparent reporting of endpoint details.

Head and neck cancer is the seventh most common type of cancer worldwide and comprise of a diverse group of tumours affecting the upper aerodigestive tract. Although many different histologies exist, the most common is squamous cell carcinoma. Predominant risk factors include tobacco use, alcohol abuse, and oncogenic viruses, including human papillomavirus and Epstein-Barr virus. Head and neck malignancies remain challenging to treat, requiring a multidisciplinary approach, with surgery, radiotherapy, and systemic therapy serving as key components of the treatment of locally advanced disease. Although many treatment principles overlap, treatment is generally site-specific and histology-specific. This Seminar outlines the current understanding of head and neck cancer and focuses on treatment principles, while also discussing future directions to improve the outcomes of patients with these malignancies.

Objective Few studies characterizing clinical outcomes of head and neck cancer (HNC) patients in sub-Saharan Africa report the proportion of patients who initiate and complete treatment, information integral to contextualizing survival outcomes. This retrospective cohort study describes HNC patients who presented to Muhimbili National Hospital and Ocean Road Cancer Institute in 2018, the highest-volume oncology tertiary referral centers in Tanzania. Logistic regression was applied to assess predictors of treatment initiation and completion. Results Among the 176 head and neck squamous cell carcinoma (HNSCC) patients, 34% (59) had no treatment documented, 34%(59) had documentation of treatment initiation but not completion, and 33%(58) had documentation of treatment completion based on the modalities started. Univariate logistic regression showed that late-stage disease was associated with increased odds of initiating treatment (OR 8.24, 95% CI 2.05–33.11, p  = 0.003) and trends toward completing treatment (OR 7.41, 95% CI 0.90–60.99, p  = 0.063). At last visit, 36.9%(65) were alive with a median follow up of 5.6 months (IQR 1.64—12.5 months). A large proportion of HNC patients who presented to MNH and ORCI did not initiate or complete treatment. These metrics are critical to contextualize care outcomes of HNC patients in resource-constrained health systems and develop interventions.

BackgroundProstate-specific membrane antigen (PSMA) is expressed in the microvasculature of thyroid cancer. This suggests the potential use of PSMA as a diagnostic agent in patients with aggressive forms of thyroid cancer. The purpose of the current study was to determine the feasibility and utility of [68Ga]Ga-PSMA-11 PET/MRI in thyroid cancer patients.MethodsEligible patients for this prospective pilot study were adults with a history of pathology-proven thyroid cancer who had abnormal radiotracer uptake on an 2-[18F]FDG PET and/or 131I scintigraphy performed in the 12 months prior to study enrollment. Patients underwent a [68Ga]Ga-PSMA-11 PET/MRI, and comparison was made to the prior qualifying 2-[18F]FDG PET CT/MRI for lesion location and relative intensity.ResultsTwelve patients underwent [68Ga]Ga-PSMA-11 PET/MRI, one of which was excluded from analysis due to debulking surgery prior to the PSMA PET. Of the remaining patients, 7/11 had differentiated disease (3 papillary, 2 follicular, 2 Hurthle cell) and 4/11 had dedifferentiated disease (2 poorly differentiated papillary, 2 anaplastic). Out of 43 lesions, 41 were visually 2-[18F]FDG positive (uptake greater than background, detection rate 95.3%) and 28 were PSMA positive (uptake greater than background, detection rate 65.1%). Uptake was heterogeneous between patients, and in some cases within patients. 3/11 patients (1 poorly differentiated papillary, 2 follicular) had PSMA uptake which was greater than FDG uptake. For the remaining 8 patients, 2-[18F]FDG uptake was greater than PSMA. Using one eligibility guideline in the prostate cancer literature for PSMA radioligand therapy (RLT), 8/11 could be considered eligible for possible future PSMA RLT. This was not predictable based on thyroid cancer subtype.Conclusions[68Ga]Ga-PSMA-11 PET demonstrated lower detection rate when compared to 2-[18F]FDG PET for thyroid cancer lesion visualization. Thyroid cancer subtype alone may not be sufficient to predict PSMA uptake, and radiotracer uptake may vary between patients and even within patients.

Background Patients with metastatic Merkel cell carcinoma (mMCC) who experience disease progression on immunotherapy have limited additional standard options. Given evidence of synergism between radiation therapy (RT) and immunotherapy, two patients progressing on PD-1 inhibition were referred for short-course RT. Case presentation Two patients were found to have progressive mMCC on PD-1 inhibitor therapy and were treated with single-fraction palliative RT. Both patients were observed to have local control at irradiated regions, as well as durable abscopal response at unirradiated, out-of-field, sites of metastatic disease. Conclusions Short-course RT is a compelling strategy that could be a means to augment response in patients with mMCC who show progression on immune checkpoint blockade. Ongoing clinical trials are investigating the relationship between RT and immunotherapy in mMCC.

Background Management of locoregional recurrence (LRR) and distant metastasis (DM) in adenoid cystic carcinoma (ACC) is guided by limited data. We investigated mortality risks in patients diagnosed and treated for recurrent ACC. Methods A retrospective review of ACC patients treated from 1989 to 2016 identified 36 patients with LRR or DM. High-risk disease was defined as skull base involvement (for LRR) or International Registry of Lung Metastases Group III/IV or extrapulmonary site of metastasis (for DM). Kaplan-Meier method, log-rank tests, and Cox proportional hazards were used for time-to-event analysis. Results Among 20 LRR and 16 DM patients, the median times to recurrence were 51 and 50 months, respectively. The median follow-up post-recurrence was 37.5 months (interquartile range (IQR)16.5–56.5). Post-recurrence 3-year overall survival (OS) was 78.5%, 73.3% for LRR and 85.1% for DM ( p  = 0.62). High-risk recurrences were associated with worse 3-year OS (68.8% for high-risk and 92.3% for low-risk, χ2 = 10.4, p  = 0.001). Among LRR patients, 90% had surgery as part of their treatment. Multimodality therapy, age, and histopathologic features (size, margins, solid histology, lymphovascular or perineural invasion) were not associated with PFS or OS. High-risk LRR was the only variable associated with OS (χ2 = 5.9, p  = 0.01). Among DM patients, six were initially managed with observation and ten received surgery, RT, or systemic therapy. Upfront therapy was not associated with improved PFS or OS. High-risk DM was the only variable associated with OS (χ2 = 4.7, p  = 0.03). Conclusions High-risk LRR and DM were associated with decreased 3-year OS. More effective therapies are needed for high-risk ACC recurrences.